2nd ECHO ASE-ASEAN: Bangkok 22nd October DR. TAN JU LE Pulmonary Hypertension Services National Heart Centre SINGAPORE
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1 2nd ECHO ASE-ASEAN: Bangkok 22nd October 2016 DR. TAN JU LE Pulmonary Hypertension Services National Heart Centre SINGAPORE
2 Definition of Pulmonary Hypertension and Cor Pulmonale Epidemiology and Pathophysiology Definition and lassification Echo imaging in Pulmonary Hypertension and Cor Pulmonale Aim of imaging Guidelines Imaging parameters to guide prognosis and treatment Other imaging modality for PHT CONCLUSION
3 Definition of PULMONARY HYPERTENSION and COR PULMONALE Epidemiology and Pathophysiology Definition and Classification
4 1. Group 1 (PAH) In Europe (ESC 2015 guidelines),pah prevalence and incidence are estimated to be and 5-10 cases per million adults respectively. Half have ipah, heritable or drug induced PAH In Associated PAH, highest prevalence is in the Connective Tissue Disease groups, mainly in patients with systemic sclerosis 2. Group 2 (PH due to LHD) 60% of HF due to impaired systolic function and 70% of HFPEF All patients with severe MV disease and 65% in those with severe AS (EHJ 2012;33:2451) 3. Group 4 (CTEPH) Spanish 2013 PH Registry: CTEPH prevalence and incidence were 3.2 and 0.9 cases per million Prevalence of 0.5-2% has been reported in survivors of acute PE (Pengo et al NEJM,2004;350;2257) International CTEP Registry: 31.9% of CTEPH patients have associated thrombophilic disorders (lupus anticoagulant/antiphospholipid antibodies, protein S and C deficiency, activated protein C resistance including factor V Leiden mutation, prothrombin gene mutation, antithrombin III deficiency and elevated factor VIII) and 3.4% had history of splenectomy.
5 French national registry Scottish Morbidity Record Scottish Pulmonary Vascular Unit Prevalence cases per million APAH, pulmonary arterial hypertension associated with other diseases or causes, in this case anorexigen; CHD-PH, congenital heart disease-associated pulmonary hypertension; CTD-PH, connective tissue disease-associated pulmonary hypertension; HIV-PH, human immunodeficiency virus-associated pulmonary hypertension; IPAH, idiopathic pulmonary arterial hypertension; PAH, pulmonary arterial hypertension; PPHTN, portopulmonary hypertension Adapted from Peacock et al. Eur Respir J. 2007;30:
6 Intimal Proliferation Adventitial Proliferation Muscular pulmonary artery from a PH patient Gaine S and Rubin L: Lancet 1998; 352: Medial Hypertrophy
7 PATHOLOGICAL FEATURES OF PULMONARY ARTERIAL HYPERTENSION Medial hypertrophy Intimal thickenning Complex lesions Plexiform lesions (black arrow) Focal proliferation of endothelium, smooth muscle cells and extracellular matrix
8 Cor Pulmonale is Right Heart Dysfunction (dilatation, hypertrophy, systolic and diastolic impairment) due to the effects of pulmonary hypertension specifically associated with diseases of the chest /lung /airway components Lung tissue (eg. COPD, interstitial lung disease, etc) Pulmonary vasculature (eg. ipah, CTEPH) Upper airway obstruction (eg. OSA) Chest wall restriction (eg. kyphoscoliosis) Right heart disease due to left-sided heart disease (Grp 2) or congenital heart disease (Grp 1.4.4) is NOT considered Cor Pulmonale Using the above definition, Cor Pulmonale is caused by some Group 1 diseases (Grp 1 but not Grp 1.4.4), Group 3 (lung), Group 4 (CTEPH) and Group 5 (Miscellaneous Grp eg. sarcoidosis) Focus on imaging in Pulmonary Hypertension and not just Cor Pulmonale
9 Previously classified into 2 types (old classification) PRIMARY PULMONARY HYPERTENSION (PPHT) SECONDARY PULMONARY HYPERTENSION Depends on presence or absence of identifiable causes PPHT diagnosis of exclusion In nd World Symposium on PAH, Evian Classification a new clinical based classification proposed to individualize different categories of PHT In in Venice, 3 rd World Symposium on PAH, modifications to Evian Classification 2008 Dana Point Update (4 th World symposium on PAH), further modifications 2013 Latest update in NICE (5 th World Symposium on PAH) 2015 ESC Guidelines on the diagnosis and treatment of Pulmonary Hypertension
10 2015 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension PULMONARY HYPERTENSION DEFINITION: PATHOPHYSIOLOGICAL Increase in mean PAP 25 mmhg at rest assessed by RHC PAH is characterised by pre-capillary PH and PVR>3 WU in the absence of other causes of precapillary PH such as due to lung disease, CTEPH, etc No data to suggest this entity PH on exercise Galie et al. EHJ ESC Guidelines Aug 2015
11 2015 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension Galie et al. EHJ ESC Guidelines Aug 2015
12 2015 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension : Pulmonary Hypertension Definition - CLINICAL
13 Group 1: Pulmonary Arterial Hypertension 1.1 Idiopathic PAH 1.2 Heritable PAH 1.3 Drug and toxin induced 1.4 Associated with Connective tissue disease HIV infection Portal hypertension Congenital heart diseases Schistosomiasis Group 1 : Pulmonary veno-occlusive disease and / or pulmonary capillary haemangiomatosis Group 1 : Persistent PH of the newborn (PPHN)
14 Group 1: Pulmonary Arterial Hypertension 1.4 Associated with Connective tissue disease HIV infection Portal hypertension Congenital heart diseases Schistosomiasis
15 1.4.1 Connective Tissue Disease The prevalence of PAH is well established only in scleroderma, and rate of occurrence is estimated between 7% and 12% The prognosis for patients with PAH associated with scleroderma remains poor and worse compared to other PAH subgroups. The 1-year mortality rate in patients with idiopathic PAH is approximately 15% (31) versus 30% in PAH-associated with scleroderma Scleroderma patients with a mean pulmonary artery pressure (PAP) between 21 and 24 mm Hg are at high risk for the development of overt PH within 3 years and should be closely followed Some data to suggest that in scleroderma, early diagnosis and early intervention may improve long-term outcome HIV infection 0.5% HIV patients develop ipah, no relationship to CD4 count or viral load Before the era of highly active antiretroviral therapy (HAART) and the development of specific PAH drugs, the prognosis for HIV-PAH was extremely poor, with a mortality rate of 50% in 1 year The advent of HAART and the wide use of PAH therapies in HIV patients have improved their prognosis, and the current survival rate at 5 years in the French cohort is more than 70% Interestingly, approximately 20% of these cases experience a normalization of hemodynamic parameters after several years of treatment Portal hypertension Hemodynamic studies have shown that PAH is confirmed in 2% to 6% of patients with portal hypertension, porto-pulmonary hypertension (POPH) and the risk of developing POPH is independent of the severity of the liver disease Long-term prognosis is related to the severity of cirrhosis and to cardiac function Congenital heart disease Schistosomiasis
16 Recommendations Class a Level b In patients with PAH associated with CTD, the same treatment algorithm as for patients with IPAH is recommended I C Resting echocardiography is recommended as a screening test in asymptomatic patients with SSc, follwed by annual screening with echocardiography, DLSO and biomarkers I C RHC is recommended in all cases of suspected PAH associated with CTD I C Oral anticoagulation may be considered on an individual basis and in the presence of thrombophilic predisposition IIb C Galiè N, et al. Eur Heart J 2016; 37:
17 2.1 Left ventricular systolic dysfunction 2.2 Left ventricular diastolic dysfunction 2.3 Valvular disease 2.4 Congenital / acquired left heart inflow / outflow tract obstruction and congenital cardiomyopathies 2.5 Congenital / Acquired pulmonary vein stenosis
18 2015 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension
19 3.1 Chronic obstructive pulmonary disease 3.2 Interstitial lung disease 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4 Sleep-disordered breathing 3.5 Alveolar hypoventilation disorders 3.6 Chronic exposure to high altitude 3.7 Developmental lung diseases
20 2015 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension
21 Chronic Thrombo-embolic Pulmonary Hypertension (CTEPH) Other pulmonary artery obstructions
22 5.1 Hematologic disorders 5.2 Systemic disorders 5.3 Metabolic disorders 5.4 Others
23 5.1 Hematologic disorders: Chronic hemolytic anemia Myeloproliferative disorders Splenectomy 5.2 Systemic disorders: Sarcoidosis Pulmonary histiocytosis, Lymphangioleiomyomatosis 5.3 Metabolic disorders: Glycogenstorage disease Gaucher disease Thyroid disorders 5.4 Others: Tumoral obstruction Fibrosing mediastinitis Chronic renal failure (with or without dialysis) Segmental pulmonary hypertension
24 Echo imaging in Pulmonary Hypertension and Cor Pulmonale Aim of echo imaging Guidelines echo in the diagnosis of PHT Imaging parameters to guide prognosis and treatment Other imaging modality for PHT
25
26 TTE is a very useful non-invasive screening tool for PHT Diagnosis, cause, severity and progression of PHT Estimate pulmonary artery systolic pressure from Doppler pattern of tricuspid (TR) and pulmonary regurgitant (PR) jet PASP = RVSP if no RVOT/PA obstruction RVSP = 4 (Vtr) 2 + RAP Assess Left Ventricular and Right Ventricular size and function Assess heart valves TR and PR, Mitral stenosis Associated congenital heart disease if any Pericardial Effusion
27
28 2015 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension
29 4 x 2.8 x = = 34 mmhg 4 x 2.9 x = = 37 mmhg 4 x 3.4 x = = 49 mmhg 4 x 3.5 x = = 52 mmhg
30 2015 ESC Guidelines on Echo probability of PHT
31 Simplified Bernoulli equation RVSP: 4 (TR Vmax) 2 + RA pressure RVSP = PASP in the absence of RVOT / pulmonary valve obstruction RA pressure or < 20% on quiet inspiration Use TR velocities for probability generation because any inaccuracies with RA pressure estimation can amplify errors
32 Is this TR measurement correct?
33 PA Diastolic Pressure PADP: 4 (End diastolic pulmonary regurgitation velocity) 2 + RA pressure Mean PAP (Masuyama) MPAP: 4 (Early diastolic pulmonary regurgitation velocity) 2 + RA pressure
34
35 Mahan s formula Using pulmonary acceleration time by pulsed Doppler of pulmonary artery in systole MPAP: 79 (0.45 x acceleration time) AT > 120ms MPAP: 90 (0.62 x acceleration time) AT < 120ms
36
37 Pulmonary vascular resistance (PVR) PRESSURE change = Flow X Resistance PVR distinguishes elevated pulmonary pressure due to high flow from that due to pulmonary vascular disease PVR can be estimated using the ratio of PVR (woods) = {TR max velocity (m/s) / RVOT VTI (in cm)} X constant This relationship is not reliable in patients with very high PVR, with measured PVR > 8 Wood units Normal PVR is <1.5 Wood units, significant PH is defined as a PVR > 3 Wood units
38 Abbas et al : JASE 2013: Volume 26 Number 10 Resistance (PVR) = PA LA Pressure difference / RV CO Simplified Method to estimate / calculate PVR by Abbas et al using TR Vmax and RVOT VTI TRV / TVI rvot = 2.78 /11 = PVR = TRV / TVI rvot x 10 = 2.53 WU
39
40 Dilated Right Ventricle Dilated Right Atrium Flatted IVS
41 Reduced LV size LV Eccentricity Index of > 1 Length/Width in ED and ES > 1 How to Measure? - Endocardium to Endocardium
42 Ratio between LV anteroposterior : septolateral dimension Ratio > 1 is abnormal Not so straight forward Dimensions are an interaction between RV and LV pressure If patient has left side heart disease, there is interplay between systolic RV pressure overload and diastolic LV pressure overload
43 W L ED = (Length) 5.3/ (Width) 2.7 = 1.96 ES= (Length) 3.1/(Width)1.0 = 3.0 Echo Report: Flattened septum in systole and diastole consistent with right ventricular pressure and volume overload LV eccentricity index (end diastole) is 1.96 and (endsystole) is 3.0
44 PA Dilated Pulmonary Artery > 25 mm (avoid measuring in an oblique angle) Dilated PA can also be seen on suprasternal view
45 RVOT PW - Mid systolic notch Short Acceleration Time
46 Dilated and Plethoric Inferior Vena Cava
47
48 LV Eccentricity Index at end diastole = 6.28/3.67 = 1.7 LV Eccentricity Index at end systole =4.15/3.03 =1.4
49
50 TDI s wave = 4.7 TAPSE = 1 (reduced)
51 Mean PAP = 32 mmhg + RAP PASP = 52 mmhg + RAP
52 Dilated and plethoric IVC, estimated RAP at least 15 mmhg Short ACT of 66 ms with mid-systolic notch present
53
54 2015 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension Follow up: For risk assessment 1. RA size RA area 2. Presence of Pericardial effusion
55 How often to do serial echo in follow up of PH patients? At baseline 6-12 monthly if no change in PH therapy 3-4 monthly after change of PH therapy
56 In reality, the survival of PH patients is determine by their Right Ventricle Function and hence serial assessment of RV function is mandatory in the echo follow up of PH patients
57 PAH : a rapidly evolving disease I Preclinical/ No symptoms II Symptomatic / Stable III Progression / declining Pulm pressure RV function Level Cardiac output Therapeutic window Years Months Time
58 Agarwal et al : Am Heart J 2011;162:
59 Other useful Imaging Modalities in PHT - VQ scan - CTPA / HRCT - CMR - PA Angiography
60 1) Ventilation Perfusion Scan (to exclude CTEPH) Maybe entirely normal VQ mismatch from normally ventilated lung with decrease perfusion in small peripheral nonsegmental pulmonary arteries VQ mismatch from chronic thromboembolic disease, the perfusion defects are more common in lobar and segmental pulmonary arteries Matched VQ defects in patients with parenchymal lung disease
61 VENTILATION VQ SCAN PERFUSION
62 2) Contrast enhanced CT / High Resolution CT Contrast enhanced spiral CT chest in patients with V/Q mismatch suggestive of thromboembolic disease Central pulmonary artery occlusion, recanalisation, stenosis High Resolution CT important for fine details of lung parenchyma Diagnosis of interstitial lung disease, emphysema Pulmonary veno-occlusive disease => central ground glass opacification and thickening of interlobular septa Pulmonary capillary haemangiomatosis => thickening of interlobular septa, small centrilobular nodular opacities Presence of lymphadenopathy, pleural effusion, etc
63 CTPA of 45 year old lady with CTEPH web web
64 High Resolution CT showing advance interstitial lung disease with honeycomb appearance
65 3) Cardiac Magnetic Resonance Imaging For both pathology and function of cardiovascular and pulmonary circulation Heart => RV and LV size and function, PA dilatation and thrombus, pulmonary and tricuspid regurgitation, shunts Thrombus RPA LPA
66 OTHER IMAGING MODALITIES IN CTEPH: PA ANGIO 4) Pulmonary angiography Selective LPA angiogram and balloon dilatation for CTEPH
67 Echocardiography can help to categorize patients with suspected PH into low, intermediate or high probabilities of PHT by using parameters such as TR velocity and assessing the effect of pulmonary hypertension on the right heart such as IVC, RA, RV and PA using 2D and Doppler measurements Some causes of PHT can be excluded by echocardiography such as Group 2 PH (due to left heart disease) and in patients with congenital heart defects and left to right shunting Other imaging modalities (such as CT, VQ, CMR) are often required to classify PH patients into the appropriate PH Groups. This is essential as current PH therapies are mainly limited to patients in Group 1 and Group 4 It is important to follow up PH patients with serial echocardiograms every 6-12 monthly or after change in therapy or with worsening symptoms Serial echocardiograms should include the assessment of pulmonary pressures, RV function and other prognostic markers such as RA size, presence of pericardial effusion, LV eccentricity index, etc
68
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